A human or higher animal peripheral nerve consists of an elongated bundle of fibers resembling an electrical cable. The nerve has an outer jacket, the epineurium, and is internally divided into sub-cables called fascicles. One nerve can include many fascicles, each one sheathed in a perineurium. The fascicles are made up of groups of nerve fibers, each fiber comprising a sheath of Schwann cells and a conductive process called the axon. A typical axon measures 20 microns or less in diameter, so that a nerve 1 mm in diameter may have 2000 axons. Each axon can transmit discrete electrical impulses like an individual insulated wire in a cable.
Nerves are defined as radiating from the brain or central nervous system--proximal--to a limb or end organ--distal. Nerve impulses are transmitted along the axons in both directions. These neural impulses, or axon depolarizations, function like the signals in a digital electronic network; they are detected as being either on or off. In the nervous system, as in a digital circuit, it is the number and frequency of the impulses, rather than their individual differences, that determine the system behavior. Human nerve impulses have a depolarization voltage of about 100 millivolts and a current density of 4-10 picoamperes per square centimeter.
The electrical signals in the nervous system are both excitatory and inhibitory. That is, depending on their source and destination, they may stimulate an action or prevent it from occurring. Both kinds of signals are transmitted through the system simultaneously. Such nerve impulses have been detected and recorded from individual axons for many years.
When a nerve is severed surgically or by accidental trauma, neural impulses cannot cross the gap. It is possible to reconnect severed nerves by microsurgical techniques. The outer sheath will heal in a few weeks, and the axons will regenerate from the proximal to the distal direction in a somewhat longer time. Electrical function will be restored in six to nine months. However, it has been shown repeatedly that even though a repaired nerve looks complete both externally and in section, the end organs served by it seldom regain more than a fraction of their original function, except in young children.
One reason for this is scale. Although the suturing of a 1 mm-diameter nerve looks to an untrained eye like fine work, it is extremely coarse compared to the structure of the nerve. To make a perfect nerve repair, one would have to connect each one of thousands of severed axons to its correct path on the opposite side of the break, a task beyond the present state of neurosurgery. In fact, following a nerve lesion the proximal axons become compartmented in many new and smaller fascicles and propagate distally in random fashion, so there is no guarantee that any of the original neural paths will be re-established. It is easily possible that a proximal axon carrying an excitatory impulse may connect to a distal path which originally received an inhibitory signal.
However, because of the organization of the nervous system, it is sometimes possible to restore partial function with a less-than-perfect repair. The system is highly redundant--that is, the same information may be transmitted simultaneously over a number of axons, any one of which is capable of activating the end organ. In many cases where a nerve was almost, but not completely severed, a high percentage of original end organ function was retained despite the greatly reduced signal path. This indicates that loss of function after repair of a completely severed nerve is due not only to the interruption of actuating impulses, but also to inhibitory mismatching when the nerve is reconnected.
The regeneration of severed axons from the proximal face is irresistible. It is led by branching probes from the Schwann cells in the axon sheath. If the two severed ends of a nerve are brought into close terminal alignment, the proximal axons will propagate through the first axon tubule they reach on the distal side of the break--not necessarily, or even probably, the correct one. The large number of mismatched axon connections after a nerve repair almost guarantees that end organ function will be seriously limited. Our invention is an attempt to correct that situation.